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Weeble mutant mice have severe locomotor instability and significant neuronal loss in the cerebellum and in the hippocampal CA1 field. Genetic mapping was used to localize the mutation to the gene encoding inositol polyphosphate 4-phosphatase type I (Inpp4a), where a single nucleotide deletion results in a likely null allele. The substrates of INPP4A are(More)
Chronic exposure to excessive manganese (Mn) is the cause of a neurodegenerative movement disorder, termed manganism, resulting from degeneration of neurons within the basal ganglia. Pathogenic mechanisms underlying this disorder are not fully understood but involve inflammatory activation of glial cells within the basal ganglia. It was postulated in the(More)
Astroglia serve as a presumptive lead (Pb) sink in the brain; therefore, this study examined Pb entry into cultured rat astroglia utilizing the Ca2+ fluorophore indo-1 as a tool for detecting Pb2+ entry during acute exposure. The interactions of Pb2+ with indo-1 were analyzed by fluorescence spectrophotometry in a cell-free system. The emission spectrum of(More)
This study examined the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and related compounds on the uptake of intracellular calcium ([Ca2+]i) in primary cultures of rat hippocampal neuronal cells. [Ca2+]i levels were detected and quantified by interactive laser cytometry with microscopic image analysis. Cells were noninvasively labeled with(More)
The EL mouse strain provides a polygenic model for epilepsy. Previous mapping experiments between EL and nonepileptic ABP mice identified, and a congenic strain confirmed, a quantitative trait locus (QTL), El2, which lowered the threshold to seizures induced by gentle rhythmic tossing. To narrow the map interval further we used a nested strategy to analyze(More)
Chronic exposure to manganese (Mn) produces a neurodegenerative disorder affecting the basal ganglia characterized by reactive gliosis and expression of neuroinflammatory genes including inducible nitric oxide synthase (NOS2). Induction of NOS2 in glial cells causes overproduction of nitric oxide (NO) and injury to neurons that is associated with(More)
The mechanisms underlying cognitive and neurobehavioral abnormalities associated with childhood exposure to manganese (Mn) are not well understood but may be influenced by neuroinflammatory activation of microglia and astrocytes that results in nitrosative stress due to expression of inducible nitric oxide synthase (iNOS/NOS2). We therefore postulated that(More)
This paper reports the results from in vitro experiments utilizing vital fluorescent probes and biochemical assays to examine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and related compounds in primary rat astroglia in an effort to identify the cellular site(s) involved in toxicity. Application of 100 nM 2,3,7,8-TCDD, a strong Ah(More)
Canine and human osteosarcoma (OSA) have many similarities, with the majority of reported cases occurring in the appendicular skeleton, gender predominance noted, high rate of metastasis at the time of presentation, and a lack of known etiology for this devastating disease. Due to poor understanding of the molecular mechanisms underlying OSA, we have(More)
The effects of lead (0.0, 0.1, or 1 microM) on subcellular sites in primary astroglial cultures were quantitated with the use of vital fluorescent probes (fluorescence bioassays). Evaluation of cellular glutathione levels with monochlorobimane revealed a reduction in glutathione content after only 7 hr of Pb treatment to 77 and 82% of control values for 0.1(More)